Seminars in Arthritis and Rheumatism 43 (2014) e2
Contents lists available at ScienceDirect
Seminars in Arthritis and Rheumatism journal homepage: www.elsevier.com/locate/semarthrit
Paradoxical relationship between TNF-alpha antagonists and sarcoidosis We read with interest the article by Russell et al. titled “Long term follow-up of efficacy of infliximab in pulmonary and extrapulmonary sarcoidosis refractory to conventional therapy.” This retrospective study holds a light to possible treatment alternatives in patients with sarcoidosis refractory to conventional treatment. However, we think that the content of this study has some debatable points. First, the relationship between TNF-alpha antagonists and sarcoidosis is known to be paradoxical. There are many reports in which TNF-alpha antagonists are claimed as a causative agent for sarcoidosis [1]. Initially, in 2002, Peno-Green et al. [2] reported a sarcoidosis case associated with etanercept treatment. In spite of many hypotheses, ongoing uncertainties for sarcoidosis etiopathogenesis make this conflict more meaningful. One of the limitations of study by Russell et al. as they mentioned, is lack of control group that arouse suspicion about this paradox. Probability of such an interaction must be questioned especially in 5.7% of infliximab treatment group in whom clinical outcomes worsened. However, lack of a control group does not lead to confrontation. The relation between sarcoidosis and mycobacteria has been introduced by too many reports in the literature [3]. Li et al. [4] showed 80% of sarcoidosis cases have mycobacterial DNA. In view of this relationship, before treatment of sarcoidosis patients with TNF-alpha antagonist, a detailed research is deemed necessary. According to materials and methods section, there has not been any research for tuberculosis before treatment. But, in one case, the treatment was terminated because of PPD conversion during infliximab therapy. We suggest that IFN-gamma release assay test, tuberculin skin test, and booster test especially in endemic areas should be performed before the treatment.
Another critical point is that benefits of infliximab were evaluated by relatively subjective methods such as clinical signs, symptoms, and radiology. There was no improvement in pulmonary function tests, which is accepted as an important prognostic factor for sarcoidosis course. So, this condition partly undermines the hypothesis of positive effect of infliximab treatment for sarcoidosis. Besides, other immunosuppressive agents were not removed, so that efficacy of infliximab therapy alone was not demonstrated clearly. This too leads to confusion regarding the effectiveness of the treatment. As a result, we suggest that further controlled clinical trials are needed to substantiate the conclusion of authors that “infliximab is efficacious in sarcoidosis.” However, the study is meaningful to be a starting point for investigations about this issue. Thanks you and the authors. References [1] Massara A, Cavazzini L, Corte RL. Sarcoidosis appearing during anti-tumor necrosis factor therapy: a new “Class Effect” paradoxical phenomenon. Two case reports and literature review. Semin Arthritis Rheum 2010;39:313–9. [2] Peno-Green L, Lluberas G, Kingsley T, Brantley S. Lung injury linked to etanercept therapy. Chest 2002;122:1858–60. [3] Saboor SA, Johnson NM, McFadden J. Detection of mycobacterial DNA in sarcoidosis and tuberculosis with polymerase chain reaction. Lancet 1992;339:1012–5. [4] Li N, Bajoghli A, Kubba A, Bhawan J. Identification of mycobacterial DNA in cutaneous lesions of sarcoidosis. J Cutan Pathol 1999;26:271–8.
Nesrin Baygin, MD,n Ergun Tozkoparan, MD Department of Chest Diseases Gulhane Military Medical Academy Ankara, Turkey E-mail address: [email protected] (N. Baygin)
n
0049-0172/$ - see front matter & 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.semarthrit.2013.11.001
Corresponding author.
Contents lists available at ScienceDirect
Seminars in Arthritis and Rheumatism journal homepage: www.elsevier.com/locate/semarthrit
Paradoxical relationship between TNF-alpha antagonists and sarcoidosis We read with interest the article by Russell et al. titled “Long term follow-up of efficacy of infliximab in pulmonary and extrapulmonary sarcoidosis refractory to conventional therapy.” This retrospective study holds a light to possible treatment alternatives in patients with sarcoidosis refractory to conventional treatment. However, we think that the content of this study has some debatable points. First, the relationship between TNF-alpha antagonists and sarcoidosis is known to be paradoxical. There are many reports in which TNF-alpha antagonists are claimed as a causative agent for sarcoidosis [1]. Initially, in 2002, Peno-Green et al. [2] reported a sarcoidosis case associated with etanercept treatment. In spite of many hypotheses, ongoing uncertainties for sarcoidosis etiopathogenesis make this conflict more meaningful. One of the limitations of study by Russell et al. as they mentioned, is lack of control group that arouse suspicion about this paradox. Probability of such an interaction must be questioned especially in 5.7% of infliximab treatment group in whom clinical outcomes worsened. However, lack of a control group does not lead to confrontation. The relation between sarcoidosis and mycobacteria has been introduced by too many reports in the literature [3]. Li et al. [4] showed 80% of sarcoidosis cases have mycobacterial DNA. In view of this relationship, before treatment of sarcoidosis patients with TNF-alpha antagonist, a detailed research is deemed necessary. According to materials and methods section, there has not been any research for tuberculosis before treatment. But, in one case, the treatment was terminated because of PPD conversion during infliximab therapy. We suggest that IFN-gamma release assay test, tuberculin skin test, and booster test especially in endemic areas should be performed before the treatment.
Another critical point is that benefits of infliximab were evaluated by relatively subjective methods such as clinical signs, symptoms, and radiology. There was no improvement in pulmonary function tests, which is accepted as an important prognostic factor for sarcoidosis course. So, this condition partly undermines the hypothesis of positive effect of infliximab treatment for sarcoidosis. Besides, other immunosuppressive agents were not removed, so that efficacy of infliximab therapy alone was not demonstrated clearly. This too leads to confusion regarding the effectiveness of the treatment. As a result, we suggest that further controlled clinical trials are needed to substantiate the conclusion of authors that “infliximab is efficacious in sarcoidosis.” However, the study is meaningful to be a starting point for investigations about this issue. Thanks you and the authors. References [1] Massara A, Cavazzini L, Corte RL. Sarcoidosis appearing during anti-tumor necrosis factor therapy: a new “Class Effect” paradoxical phenomenon. Two case reports and literature review. Semin Arthritis Rheum 2010;39:313–9. [2] Peno-Green L, Lluberas G, Kingsley T, Brantley S. Lung injury linked to etanercept therapy. Chest 2002;122:1858–60. [3] Saboor SA, Johnson NM, McFadden J. Detection of mycobacterial DNA in sarcoidosis and tuberculosis with polymerase chain reaction. Lancet 1992;339:1012–5. [4] Li N, Bajoghli A, Kubba A, Bhawan J. Identification of mycobacterial DNA in cutaneous lesions of sarcoidosis. J Cutan Pathol 1999;26:271–8.
Nesrin Baygin, MD,n Ergun Tozkoparan, MD Department of Chest Diseases Gulhane Military Medical Academy Ankara, Turkey E-mail address: [email protected] (N. Baygin)
n
0049-0172/$ - see front matter & 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.semarthrit.2013.11.001
Corresponding author.
